April 27, 2026

Top News
FDA Approves Caplyta for Schizophrenia Relapse Prevention, Citing 63% Risk Reduction
Substance Use
A single dose of psilocybin outperforms nicotine patches for quitting smoking - PsyPost

A single dose of psilocybin demonstrates superior efficacy compared to nicotine patches for smoking cessation, highlighting a novel pharmacologic approach to substance use disorder treatment.

Policy & Regulation
FDA Approves sNDA of Caplyta for the Prevention of Relapse in Schizophrenia - Psychiatric Times

The FDA has approved a supplemental new drug application for Caplyta (lumateperone) to prevent relapse in schizophrenia, expanding its approved indication for this atypical antipsychotic.

Policy & Regulation
Lumateperone sNDA Approved with Relapse Prevention Data in Schizophrenia - HCPLive

The FDA has approved the supplemental new drug application for lumateperone, establishing its efficacy for relapse prevention in schizophrenia based on new clinical data.

Policy & Regulation

The FDA has approved a supplemental New Drug Application for lumateperone (Caplyta) to prevent relapse in schizophrenia, based on Phase 3 data showing a 63% reduction in relapse risk and a favorable metabolic and prolactin profile over 6 to 12 months.

Clinical Pearl
Concurrent SSRI, SNRI, or Other Antidepressant Use Not Associated With Differential Outcomes in Ketamine or Esketamine Treatment

Concurrent use of SSRIs, SNRIs, or other antidepressants does not significantly alter the clinical response or remission rates in patients receiving ketamine or esketamine for treatment-resistant depression.

Clinical Pearls

Bite-sized clinical takeaways from today's literature (sources from Jan 23 – Apr 27)

  • Utilize the newly approved indication for lumateperone (Caplyta) to prevent relapse in schizophrenia, leveraging its favorable metabolic and prolactin profile for long-term maintenance.
  • Proactively monitor metabolic parameters and consider weight-neutral alternatives or adjunctive strategies like olanzapine/samidorphan for patients on high-risk antipsychotics, given the 33% obesity incidence in schizophrenia.
  • Maintain milnacipran rather than switching to sertraline/quetiapine in pregnant patients with severe PTSD or psychotic depression to prevent rapid symptom relapse, as maternal stability is critical.
  • Exercise immediate vigilance for venous thromboembolism in patients initiating antipsychotic polypharmacy, as rare early-onset pulmonary embolism can occur even without traditional risk factors.
  • Continue concurrent SSRIs or SNRIs in patients receiving ketamine or esketamine for treatment-resistant depression, as these combinations do not significantly alter clinical response or remission rates.
  • Consider elevated glutamine levels as a potential biomarker to assist in determining clozapine eligibility for early psychosis patients.
  • Leverage the PETRUSHKA digital tool to enhance antidepressant continuation rates and improve medication adherence in patients with depression.
  • Assess right frontal pole engagement via TMS targeting to predict antidepressant response in patients with major depressive disorder.
  • Consider psilocybin as a novel pharmacologic option for smoking cessation, as it has demonstrated superior efficacy compared to nicotine patches in preliminary studies.
  • Monitor for polygenic risk score influences on antipsychotic responsiveness in schizophrenia, particularly in patients with comorbid ADHD or ASD traits, to tailor treatment outcomes.

Policy & Regulation 2

Compass, Usona and Transcend score FDA national priority vouchers amid Trump administration’s psychedelic push - Fierce Biotech

Three companies received FDA priority review vouchers for their psychedelic drug candidates, signaling a potential shift in regulatory support under the current administration.

FDA awards priority vouchers to 3 undisclosed companies for investigational psychedelics - BioSpace

The FDA awarded priority review vouchers to three undisclosed companies for investigational psychedelics, signaling regulatory interest in this class of psychotropic agents despite the specific indications and drug names remaining confidential.

Clinical Pearl 3

Case Report: Early onset pulmonary embolism following antipsychotic polypharmacy in an acute psychiatric setting

A case report highlights a rare, early-onset pulmonary embolism within hours of initiating antipsychotic polypharmacy, underscoring the need for immediate vigilance for VTE even in patients without traditional risk factors.

InvestigateTV+: First responders with PTSD are turning to Arizona’s psilocybin trial - KBTX News 3

First responders with PTSD are participating in a clinical trial of psilocybin in Arizona, representing a potential new treatment avenue for this high-risk population.

736. Large-Scale, Real-World Clinical Outcomes in Intravenous (IV) Racemic Ketamine Infusions for Major Depressive Disorder and Bipolar Disorder

Real-world data from a large-scale study evaluates the clinical outcomes of intravenous racemic ketamine infusions for major depressive disorder and bipolar disorder.

Diagnosis & Treatment 5

In the Land of the Unblind: are psychedelics really better than antidepressants?

This article critiques the comparative efficacy of psychedelic therapy versus antidepressants by highlighting the confounding influence of the placebo effect in unblinded trials.

Milnacipran continuation during pregnancy in a patient with severe post-traumatic stress disorder and psychotic depression: a case report with 3-year pediatric follow-up

This case report highlights the critical importance of maintaining milnacipran for maternal stability in severe PTSD and psychotic depression during pregnancy, as switching to sertraline and quetiapine resulted in rapid symptom relapse, while the infant showed no adverse developmental outcomes at 3-year follow-up.

Acceptability of cannabidiol as a treatment for people at clinical high risk for psychosis

A survey of individuals at clinical high risk for psychosis indicates high acceptability and willingness to use cannabidiol (CBD) as a treatment, with most preferring tablet or capsule formulations.

Why Feeling Good is Harder than Not Feeling Bad

The article discusses Positive Affect Treatment (PAT) as a therapeutic approach to rebuild the brain's reward system for reducing depression, anxiety, and suicide risk.

Comparative effectiveness of treatment strategies for bipolar disorder during and after lithium treatment - Nature

A Nature study compares the effectiveness of various treatment strategies for bipolar disorder during and after lithium therapy, providing evidence for clinical decision-making in mood stabilization.

Journal Article 1

A meta-analysis of the incidence proportion of obesity and associated risk factors in patients with schizophrenia

This meta-analysis quantifies the 33% obesity incidence in schizophrenia and identifies olanzapine and combined antipsychotic regimens as major modifiable risk factors, supporting proactive metabolic monitoring and drug selection.

Pharmacogenomics 1

Genetic risk for neurodevelopmental disorders as a potential factor affecting antipsychotic responsiveness in schizophrenia: a postmortem brain study

A postmortem study suggests that polygenic risk scores for ADHD and ASD may influence antipsychotic responsiveness in schizophrenia, highlighting potential pharmacogenomic implications for treatment outcomes.

Digital Health 1

PETRUSHKA Tool Improves Antidepressant Continuation, With Andrea Cipriani, MD, PhD - HCPLive

The PETRUSHKA tool enhances antidepressant continuation rates, offering a digital intervention to improve medication adherence in depression treatment.

Drug Development 1

Depression treatment is shifting, and this mushroom-derived compound is driving one of psychiatry's biggest new tests

The article introduces a mushroom-derived compound as an emerging treatment option for depression, signaling a shift in therapeutic approaches beyond traditional SSRIs and SNRIs.

Mechanism of Action 3

Loss of connexin 36 elicits abnormalities in thalamocortical network activity relevant to neuropsychiatric disorders

This study identifies connexin 36 as a critical regulator of thalamocortical synchrony and proposes it as a novel therapeutic target for modulating network dysfunction in schizophrenia.

Elevated glutamine but not glutamate is associated with clozapine eligibility in an early psychosis sample - Frontiers

Elevated glutamine levels, distinct from glutamate, are identified as a potential biomarker for clozapine eligibility in early psychosis patients.

734. TMS-Induced Antidepressant Response is Linked to Engagement of the Right Frontal Pole

This study identifies engagement of the right frontal pole as a key neural correlate predicting antidepressant response to Transcranial Magnetic Stimulation (TMS).

Neuroscience 1

741. Anterior Insula Subregional Disruptions Within the Threat Network in PTSD

This fMRI study identifies specific disruptions in the functional connectivity of anterior insula subregions within the threat network in PTSD, highlighting distinct hemispheric patterns that may inform future neuromodulation targets.